Project 1: Biomarkers of Chemical Exposure and Leukemia Risk This project builds upon the existing Northern California Childhood Leukemia Study (NCCLS), a large case-control study with over 1,000 cases. Its overall goal is to determine the role exposure to environmental chemicals plays in the etiology of childhood leukemia. We aim to examine the potential role benzene, polycyclic aromatic hydrocarbons (PAH) and other selected Superfund chemicals, such as trichloroethylene (TCE), play in the etiology of childhood leukemia in California. We will use state-of-the-art exposure assessment techniques to accomplish this goal. We further propose to use gene expression profiling and proteomics to develop new biomarkers that aid in the classification of etiologic subtypes of this disease and help find its cause(s). Our hypothesis is that certain subtypes of leukemia will have specific environmental causes. Specifically, we plan to: 1) Extend case ascertainment through 2009, such that biological samples will be available from over 1000 cases;2) characterize the childhood leukemia cases by proteomics and gene expression profiling;3) collaborate with the CDC to measure more than 30 volatile hydrocarbons in the blood of mothers of children with leukemia and control mothers (we will compare these measures with results from concomitant home air and water sampling and with surrogate markers of past exposures to VOCs using self-reported exposure to tobacco smoke and estimated traffic density);4) measure protein adducts of benzene and naphthalene (a representative PAH) in serum from mothers of cases and controls in collaboration with Dr. Rappaport of the North Carolina SBRP;and, 5) measure protein adducts of benzene and naphthalene in the plasma of children with different forms of leukemia and correlate these measurements with the chemical exposure analysis conducted with household samples. The strengths of the study are: a) Large sample size;b) extensive residential exposure assessment;c) measures of current and cumulative exposure to Superfund chemicals in both case and control mothers and children;d) ability to compare exposures to national NHANES data;e) availability of carefullyprocessed biological samples;and, f) application of sophisticated -omic technologies to case characterization. These studies should provide new insights into the role of chemical exposure in the etiology of childhood leukemia and produce new biomarkers of exposure and disease status that can be used in future studies.